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Color Blindness Gene Therapy
Colorblindness Colorblindness is a genetic disorder affecting 1 in 10 men. It is characterized by an inability to see distinct colors in the way the average human does. The eye contains two types of cells in the retina: rods and cones. Rod photoreceptor cells detect light and dark gradients and are responsible for our peripheral vision; cone photoreceptors detect three distinct types of colors (1; 2). Nearly 6 million cone photoreceptors are found in the central retina, of which there are three types: L cones (long), M cones (middle), S cones (short) (5). L cones absorb orange light best, while M cones absorb yellowish-green light, and S cones blue-violet light (2). Genetically, colorblindness entails the deleted or mutated gene encoding for one of these types of cones. The gene loci for the three cones is very polymorphic and is found on the X-chromosome; the disorder nearly always affects males (1; 2). Humans, along with many other animals, are considered trichomats, or organisms that posses three types of cones, therefore seeing three types of colors that result in our color vision. Dichromatism, or the expression of only two of the photoreceptor genes, is the cause of partial colorblindness. Those who are lacking the L cone gene are considered to have protoanopia; those lacking the M cone gene have deuteranopia; and those lacking the S cone gene have tritanopia, the most rare of the three (2; 3). Gene Therapy in Animal Models The goals of gene therapy for colorblindness are to restore trichromatic vision to those affected by the disorder. Although this has never been demonstrated in humans, based on the results from animal trials, it is possible to perform. Essentially, the gene for the photopigment the patient lacks is inserted into the sub-retinal space of the eye, where cone photoreceptors will express the newly introduced gene (2). To get the gene into the central retina to be expressed, researchers have used a viral vector. The genome of a single stranded adeno-associated virus is manipulated, resulting in a recombinant version of the virus (rAAV). Inserted into this rAAV is the fully functioning gene of choice, most often the complementary DNA encoding for M or L cones. This gene is regulated by recombinant human L and M-opsin promoters and enhancers, which allow the gene to be expressed in specific cone photoreceptor cells (3; 4). In animal trials involving adult squirrel monkeys and Mongolian gerbils, trichromatic vision was restored in both animals. It took several weeks for results to become apparent. It was determined that only about 40% of the cones can be safely transduced with the amount of rAAV that was inserted into the sub-retinal space. Gene therapy for colorblindness in animal models has been considered a success (3; 4). Controversies and Consequences As of 2014, the only experiments regarding restoring color vision have been performed on animal models (2). Because only a single gene encodes for the photopigment that is lacking in a partially colorblind individual, this gene therapy is considered very easy to perform compared to other, more invasive therapies. That being said, the question many scientists have proposed is whether or not the therapy is worth it in the long run (2). Some scientists have debated that partial colorblindness is not a disability, considering how so many partially colorblind people live normal lives. This form of gene therapy cannot treat non-retinal forms of colorblindness, such as certain other genetic disorders and brain injury-related blindness. In addition, it is not known how frequently the genes must be injected to sustain results; it is possible the rAAV may induce an immune response to the virus after long-term injections. Lastly, the genes must be injected directly into the sub-retinal area, a process that may be extremely unpleasant and risk infection (2). References 1) Color blindness. U.S. National Library of Medicine. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001997/. Updated May 7, 2013. Accessed October 12, 2014. 2) Gene therapy for colorblindness. Wikipedia. http://en.wikipedia.org/wiki/Gene_therapy_for_color_blindness. Updated August 31, 2014. Accessed October 12, 2014. 3) Mancuso K, Hauswirth WW, Li Q, et. al. Gene therapy for red-green colour blindness in adult primates. Nature. October 8, 2009; 461(7265): 784-787. doi: 10.1038/nature08401 4) Mauck MC, Mancuso K, Kuchenbecker JA, et. al. Longitudinal evaluation of expression of virally delivered transgenes in gerbil cone photoreceptors. Visual Neuroscience. March 18, 2008; 25: 273-282. doi: 10.10170S0952523808080577 5) Alexander JJ, Umino Y, Hauswirth WW. Restoration of cone vision in a mouse model of achromatopsia. Nat Med. June 2007; 13(6): 685-687. doi: 10.1038/nm1596